INTRODUCTION: Governance of COVID-19 responses has been challenging for all countries. Syria has been particularly challenged due to protracted multiparty conflict and debilitated health systems fragmented across different areas of control. To improve response governance, better understanding of frontline response policy implementation across the country is needed. This study thus explored perspectives of COVID-19 response governance among frontline healthcare providers over time and across major areas of control. METHODS: We used a qualitative longitudinal study design, conducting five rounds of remote semistructured interviews in Arabic (ie, approximately eight interviews each in March 2020, July 2020, September 2020, December 2020 and September 2021) with 14 purposively sampled public and private healthcare providers in the three main areas of control (ie, opposition-controlled area, Autonomous Administration-controlled area and al-Assad government-controlled area (GCA)). We conducted integrative thematic analysis in Arabic within and across geography and time. RESULTS: Almost all participants across all areas and rounds expressed distrust of local health authorities and dissatisfaction with COVID-19 response governance. This was most apparent in initial rounds and in GCA. Response planning was identified as insufficient, non-participatory and non-transparent. Limited infrastructure and resources were the main challenges across time, though anticipated rapid virus spread and health systems' collapse did not occur and participant optimism increased over time. Public adherence to prevention measures varied-initially weak due to general scepticism, increasing after first cases were confirmed and then fluctuating with case numbers and challenges of insecurity and misinformation. Perceptions of COVID-19 vaccination varied, with low uptake and hesitancy attributed to misinformation, disinformation and disinterest. Suggested improvements to COVID-19 response governance focused on strengthening health systems' capacity and coordination. CONCLUSION: This is a unique longitudinal study of COVID-19 responses. Addressing transparency and misinformation should be a first step to improving public engagement and trust and thus response governance for health emergencies in Syria.